The Environmental Genome Project of DIR is still completing the list of submitted genes for single nucleotide polymorphisms (SNPs) by resequencing known genes in a population of ninety-six normal individuals. This project is to be replaced by an extramural effort to complete a larger array of genes with identification of the entire genomic sequence including intronic regiona. This new effort is based upon the success of the DIR program as well as on two sequencing grants from the NIEHS extramural program. During this fourth year of funding we have continued an Interagency Agreement for discovering common polymorphisms with Lawrence Livermore National Laboratory, (Department of Energy)under the direction of Dr. Harvey Mohrenweiser. The human cell lines were obtained from the Coriell Institute. This program will end with completion of SNP analysis in the exons of approximately 50 genes. The complete SNP data can be accessed on the egSNP database found on the NIEHS Website. This information will also be uploaded to dbSNP (NCBI). It is becoming increasingly clear that relative susceptibility of individuals and groups to medicines and toxicants are to some degree dictated by the subtle differences in gene sequences, which in turn may produce proteins with altered ability to metabolize or attach to intended substrates. This phenomenon can result in an individual being more or less sensitive to environmental toxicants or pharmaceuticals. Understanding these variations can greatly help both formulation of new medicines and aid in developing prevention strategies for exquisitely sensitive individuals.